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Carcinogenicity

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Description of key information

No carcinogenicity study with Fatty acids, C14 -18 and C16 -18 unsatd., zinc salts is available, thus the carcinogenicity will be addressed with existing data on the moieties liberated upon dissolution, zinc and fatty acids, C14 -18 and C16 -18 unsatd. Fatty acids, C14 -18 and C16 -18 unsatd., zinc salts is not assumed to be a carcinogen, since the two moieties zinc and fatty acids, C14 -18 and C16 -18 unsatd. are not able to induce hyperplasia or pre-neoplastic lesions (see section on repeated dose toxicity) nor is it classified or assumed to show any mutagenic response in vitro or in vivo.

Key value for chemical safety assessment

Carcinogenicity: via oral route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Carcinogenicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Carcinogenicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Fatty acids, C14 -18 and C16 -18 unsatd., zinc salts is not assumed to be a carcinogen, since there is no evidence for an intrinsic carcinogenicity of the two moieties zinc and fatty acids, C14 -18 and C16 -18 unsatd.

Thus, Fatty acids, C14 -18 and C16 -18 unsatd., zinc salts is not to be classified according to regulation (EC) 1272/2008 and its subsequent amendments as carcinogenic.

Additional information

Fatty acids, C14 -18 and C16 -18 unsatd., zinc salts

Fatty acids, C14 -18 and C16 -18 unsatd., zinc salts is not assumed to be a genotoxic carcinogen, since the two moieties liberated upon dissolution, zinc and fatty acids, C14 -18 and C16 -18 unsatd., have not shown gene mutation potential in bacteria and mammalian cells and clastogenicity was also not observed in vitro.

There are a range of epidemiological studies that investigated the association between zinc exposure either through occupational activities or food supplementation and increased cancer risks. While no associations were found between occupational zinc exposure and excess cancer risk, the main association that has been made in this context is related to dietary/supplemental zinc and prostate cancer risk. Costello et al.,concluded that epidemiological studies have not provided an established relationship for any effect or lack thereof of dietary/supplemental zinc on the risk of prostate cancer. There is no evidence on a carcinogenic potential of the moiety fatty acids C14 -18 and C16 -18 unsatd. Due to their innocuous nature, fats and oils are commonly used as controls and as vehicles in animal toxicity studies including carcinogenicity studies.

Additionally, the moiety fatty acids, C14 -18 and C16 -18 unsatd. is obtained from natural sources and excluded from the obligation to register. Furthermore, there is no indication that the moiety zinc and fatty acids, C14 -18 and C16 -18 unsatd. induce hyperplasia or pre-neoplastic lesions.

Read-across approach and conclusion are also in line with the EU risk assessment carried out on the structurally similar substance Fatty acids, C16-18, zinc salts (i.e. zinc stearate) within the framework of EU Existing Chemicals Regulation 793/93 (EU RAR Zinc stearate (CAS# 91051-01-3, CAS# 557-05-1) Part II–Human Health. EUR 21168 EN (http://echa.europa.eu/documents/10162/08799aec-42c5-44e0-9969-baa022c66db1):

"The available data are limited. Zinc deficiency or supplementation may influence carcinogenesis, since promoting and inhibiting actions have been reported. However, there is no clear experimental or epidemiological evidence for a direct carcinogenic action of zinc or its compounds. "

Further testing is not required.

Please refer to the respective assessment entity section for data on the moieties zinc and fatty acids, C14 -18 and C16 -18 unsatd. In brief:

Zinc

There are a range of epidemiological studies that investigated the association between zinc exposure either through occupational activities or food supplementation and increased cancer risks. While no associations were found between occupational zinc exposure and excess cancer risk, the main association that has been made in this context is related to dietary/supplemental zinc and prostate cancer risk.

In contrast to established clinical and experimental evidence that prostate cancer is associated with a decrease in the zinc uptake, numerous epidemiology studies and reports of the effect of dietary and supplemental zinc on the incidence of prostate cancer have provided divergent, inconsistent and inconclusive results which range from adverse effects of zinc, protective effects of zinc and no effect of zinc on the risk of prostate cancer. Clinical and experimental studies have established that zinc levels are decreased in prostate cancer and support a role of zinc as a tumor suppressor agent. Malignant prostate cells in situ are incapable of accumulating high zinc levels from circulation (Franklin et al.,2005; Costello and Franklin, 2006; Franklin and Costello, 2007).

In a recent critical assessment of epidemiology studies regarding dietary/supplemental zinc and prostate cancer risk, Costello et al. concluded that epidemiological studies have not provided an established relationship for any effect or lack thereof of dietary/supplemental zinc on the risk of prostate cancer. Proclamations of an association of dietary/supplemental zinc and increased prostate cancer are based on inconclusive and uncorroborated reports (Costello et al.,2007). On the basis of the existing information it can be concluded that there is no conclusive evidence for carcinogenic activity of any of the zinc compounds considered in this chemical safety report.

 

Fatty acids, C14 -18 and C16 -18 unsatd.

Fatty acids, C14-18 and C16-18 unsatd., zinc salts is a mixture naturally occurring C14-18 saturated and C16-18 unsaturated fatty acids. They are naturally produced by a wide range of plants and organisms. They are naturally present in butter, cheese, milk and meat and some of them are common food additives or involved in essential biochemical processes. Thus, the following endpoint is covered by publicly available data on fatty acids with the same or similar structure.

According to a very recent ECHA report, non-branched aliphatic fatty acids (C5-C24) “are expected to be of low toxicity by their nature (similar to high purity fatty acids of natural origin which do not need to be registered as included in Annex V to REACH). […] From a human health perspective, substances in this group are considered to have a low systemic toxicity profile with no specific target organ toxicity or CMR properties. Some have irritant and/or corrosive properties that are reflected in the classification and labelling. Risk from these properties can be avoided by implementing risk management measures in supply chains based on the correct classification and labelling products. Therefore, there is no need for further action on the substances belonging to the group of aliphatic fatty acids non-branched (C5-C24)” (ECHA, 2020: Integrated Regulatory Strategy Annual Report May 2020).

 “In a two year study by Hiasa et al. (1985), groups of 50 male and 50 female F344 rats, initially 7 weeks old, were given sodium oleate (C18) for 108-weeks at concentrations of 2.5 and 5.0% in the drinking water. Control rats were given distilled water only. Sodium oleate slightly reduced the body-weight gain in the males, but not in the females, while water consumption was slightly depressed in the females, but not in the males. A slight depression in serum bilirubin of males in the 5.0% group was the only statistically significant finding (p<0.05) in the serum and urine analyses and in the haematological determinations of treated and control groups. In the groups given 5% sodium oleate, the mean weights of the liver of males and of the heart, pancreas and adrenals of females were significantly lower (p<0.05) than those of the respective controls, while the weight of the thymus in the females was significantly higher (p<0.05). Tumours developed in various organs, but there was no significant difference between their incidence in oleate-treated and control rats, apart from the pancreatic tumours (0% - 0/41M, 1/43F; 2.5% - 4/40M, 1/39F; 5% - 7/45M, 1/45F). However, the incidence of pancreatic tumours was within the normal background level for this strain of rat and the result was attributed to the unusual absence of pancreatic tumours in the control rat. Based on a weight of evidence approach including consideration of the historical range of pancreatic tumours in these rats it was concluded that sodium oleate does not induce tumours when given orally to rats (Hiasa at al. 1985)” (HERA, 2002 and references therein).

“No evidence of carcinogenicity was seen in rats receiving 25% oleic acid (C18) in the diet (approximately 12.5 g/kg bodyweight per day) for 20 weeks” (HERA, 2002 and references therein).

“Also, due to their innocuous nature, fats and oils are commonly used as controls and as vehicles in animal toxicity studies. This along with the long history of safe use of the fatty acids and their salts, as well as the GRAS status (Generally Recognised as Safe (GRAS) by the U.S. Food Drug Administration (US FDA)) for many of these chemicals, indicate no potential for carcinogenicity of these chemicals” (HERA, 2002 and references therein).

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